DE602004012712T2 - PHOSPHIN COMPOUND, INTERMEDIATE COMPOUND, PALLADIUM COMPLEX AND THEIR USE - Google Patents

Abstract

Palladum-phosphine complexes obtained by reacting a 5 compound of formula (1) below with a palladium compound: F(I) (wherein R<SUP>1 </SUP>is a hydrogen atom, an alkyl group, a cycloalkyl group or a phenyl group which may be substituted; R<SUP>2 </SUP>and R<SUP>3 </SUP>are each, the same or different, an alkyl group, a cycloalkyl group or a phenyl group which may be substituted; R<SUP>4 </SUP>and R<SUP>5 </SUP>are each, the same or different, a hydrogen atom, an alkyl group, a cycloalkyl group or a phenyl group which may be substituted; R<SUP>6</SUP>, R<SUP>7</SUP>, R<SUP>8 </SUP>and R<SUP>9 </SUP>are each, the same or different, an alkyl group, a cycloalkyl group, a phenyl group which may be substituted, an alkoxyl group, a dialkylamino group, a halogen atom, a phenyl group, a benzyl group, a naphthyl group or a halogenated alkyl group; R<SUP>6 </SUP>and R<SUP>7</SUP>, R<SUP>8 </SUP>and R<SUP>9 </SUP>may be combined to form, each, a fused ring, a trimethylene group, a tetramethylene group or a 20 methylenedioxy group; p, q, r and s are each an integer of 0 to 5; and p+q, and r+s are each in the range of 0 to 5.), which is a novel and efficient catalyst for manufacturing various useful compounds

Description

Technical area

The The present invention relates to a phosphine compound and a palladium-phosphine complex, by treating the phosphine compound with a palladium compound available is. The present invention also relates to a manufacturing method of unsaturated Compounds or aromatic compounds using the Palladium-phosphine complex as a catalyst.

Background Art

Currently, many transition-metal complexes are used as catalysts for organic synthesis reactions, see EP-A-690065 , It is well known that the ligand, together with the transition metals as central metals, plays an important role as a factor for the full utilization of the performance or activity of these catalysts. For example, many phosphine compounds have been developed as ligands and as such have played a key role.

The most important is the formation of an optimal catalyst for each of various types of reaction and substrate. The combination of Central metal and the phosphine ligand, which form the catalyst, however, is so complex that the known phosphine ligands may be insufficient in some cases without them, for example enough catalytic activity for the Use in practical industrial production. Consequently, the development of excellent new phosphine ligands is still very much desired.

Disclosure of the invention

Accordingly, that is Object of the invention to provide a new ligand, the for various catalytic Reactions is usable, and moreover the provision by the catalysts containing this ligand to be used, a process for producing unsaturated Compounds used as intermediates of medicinal and organic electronic materials are important.

The relevant inventors have, after intensive studies, the above to solve the mentioned problem, found that one new phosphine compound with a cyclopropane component an excellent ligand is and that the Complex of this new phosphine compound with a palladium compound as a catalyst for the synthesis of unsaturated or aromatic compounds extremely effective is what the efficient production of unsaturated or aromatic compounds, in particular aromatic compounds, allows, and so the present Invention completed.

• TOPOLSKI, M. et al., Journal of Organic Chemistry (1993), 58(3), 546–55, 1993;
• WALBORSKY, H. M. et al., Tetrahedron Letters (1985), 26(23), 2743–6, 1985;
• BOCHE, G. et al., Journal of American Chemical Society (1980), 102(17), 5697–9, 1980;
• LUCKENBACH, Reiner et al., Zeitschrift fuer Naturforschung, Teil B: Anorganische Chemie, Organische Chemie (1979) 34B(3), 464–80, 1979;
• SANDER, Volker et al., Chemische Berichte (1978), 111(12), 3879–91, 1978;
• WALBORSKY, H. M. et al., Journal of Organometallic Chemistry (1973), 51, 55–75, 1973;
• WALBORSKY, H. M. et al., Journal of Organometallic Chemistry (1973), 51, 31–53, 1973;
• WALBORSKY, Harry M. et al., Journal of the American Chemical Society (1971), 93(3), 671–5, 1971;
• HAUSSER, Jack W. et al., Journal of the American Chemical Society (1967), 89(26), 6981–4, 1967.

bekannt.Intermediates for preparing the phosphine compound having a cyclopropane main chain mentioned above are:

• TOPOLSKI, M. et al., Journal of Organic Chemistry (1993), 58 (3), 546-55, 1993;
• WALBORSKY, HM et al., Tetrahedron Letters (1985), 26 (23), 2743-6, 1985;
• BOCHE, G. et al., Journal of American Chemical Society (1980), 102 (17), 5697-9, 1980;
• LUCKENBACH, Reiner et al., Zeitschrift fur Naturforschung, Part B: Inorganic Chemistry, Organic Chemistry (1979) 34B (3), 464-80, 1979;
• Sander, Volker et al., Chemische Berichte (1978), 111 (12), 3879-91, 1978;
• WALBORSKY, HM et al., Journal of Organometallic Chemistry (1973), 51, 55-75, 1973;
• WALBORSKY, HM et al., Journal of Organometallic Chemistry (1973), 51, 31-53, 1973;
• WALBORSKY, Harry M. et al., Journal of the American Chemical Society (1971), 93 (3), 671-5, 1971;
• HAUSSER, Jack W. et al., Journal of the American Chemical Society (1967), 89 (26), 6981-4, 1967.

known.

• 1. eine Phosphinverbindung der Formel (1),
  
  worin R¹ ein Wasserstoffatom, eine Alkylgruppe, eine Cycloalkylgruppe oder eine Phenylgruppe, die substituiert sein kann, ist; R² und R³, jeweils gleich oder verschieden, eine Alkylgruppe, eine Cycloalkylgruppe oder eine Phenylgruppe, die substituiert sein kann, sind; R⁴ und R⁵, jeweils gleich oder verschieden, ein Wasserstoffatom, eine Alkylgruppe, eine Cycloalkylgruppe oder eine Phenylgruppe, die substituiert sein kann, sind; R⁶, R⁷, R⁸ und R⁹, jeweils gleich oder verschieden, eine Alkylgruppe, eine Cycloalkylgruppe, eine Phenylgruppe, die substituiert sein kann, eine Alkoxylgruppe, eine Dialkylaminogruppe, ein Halogenatom, eine Benzylgruppe, eine Naphthylgruppe oder eine halogenierte Alkylgruppe sind; R⁶ und R⁷ oder R⁸ und R⁹ jeweils unter Bildung eines kondensierten Rings, einer Trimethylengruppe, einer Tetramethylengruppe oder einer Methylendioxygruppe kombiniert werden können; p, q, r und s jeweils eine ganze Zahl von 0 bis 5 sind; und p + q und r + s jeweils im Bereich von 0 bis 5 liegen;
• 2. einen Palladium-Phosphin-Komplex, der durch Umsetzen der oben in 1 genannten Phosphinverbindung mit einer Palladiumverbindung erhalten werden kann;
• 3. den oben in 2 genannten Palladium-Phosphin-Komplex, wobei die Palladiumverbindung ein Palladiumsalz oder ein Palladiumkomplex ist, wobei die Valenz von Palladium 4, 2 oder 0 ist;
• 4. ein Herstellungsverfahren einer ungesättigten Verbindung oder einer aromatischen Verbindung unter Verwendung der oben in 2 oder 3 genannten Palladium-Phosphin-Komplexe als Katalysator;
• 5. ein Herstellungsverfahren einer ungesättigten Verbindung oder einer aromatischen Verbindung unter Verwendung der oben in 1 genannten Phosphinverbindung und einer Palladiumverbindung;
• 6. das oben in 4 oder 5 genannte Herstellungsverfahren, welches das Umsetzen einer Verbindung der nachstehenden Formel (3) oder (4): Ar¹(X¹)m¹ (3)
  
  wobei in Formel (3) Ar¹ eine Arylgruppe, die substituiert sein kann, oder eine Heteroarylgruppe, die substituiert sein kann, ist; X¹ ein Chloratom, ein Bromatom, ein Iodatom, eine Trifluormethansulfonyloxygruppe, eine Methansulfonyloxygruppe oder eine para-Toluolsulfonyloxygruppe ist und m¹ eine ganze Zahl von 1 bis 4 ist, und in Formel (4) R¹⁰¹, R¹¹¹ und R¹²¹, jeweils gleich oder verschieden, ein Wasserstoffatom, eine Alkylgruppe, eine Arylgruppe, die substituiert sein kann, eine Heteroarylgruppe, die substituiert sein kann, eine Alkoxycarbonylgruppe oder eine Cyanogruppe sind; X¹¹ ein Chloratom, ein Bromatom, ein Iodatom, eine Trifluormethansulfonyloxygruppe, eine Methansulfonyloxygruppe oder eine para-Toluolsulfonyloxygruppe ist, mit einer Verbindung der nachstehenden Formel (5) oder (6), Ar²X² (5)
  
  wobei in Formel (5) Ar² eine Arylgruppe, die substituiert sein kann, oder eine Heteroarylgruppe, die substituiert sein kann, ist; X² B(OR¹³)(OR¹⁴), Sn(R¹⁵)₃, MgX, ZnX, Al(R¹⁵)₂ oder Li ist, und in Formel (6) R¹⁰, R¹¹ und R¹², jeweils gleich oder verschieden, ein Wasserstoffatom, eine Alkylgruppe, eine Arylgruppe, die substituiert sein kann, eine Heteroarylgruppe, die substituiert sein kann, eine Alkoxycarbonylgruppe oder eine Cyanogruppe sind; R¹⁰ und R¹² unter Bildung einer Einfachbindung, die zusammen mit der vorhandenen Doppelbindung eine Drei fachbindung bildet, kombiniert werden können; X³ ein Wasserstoffatom, B(OR¹³)(OR¹⁴), Sn(R¹⁵)₃, MgX, ZnX, Al(R¹⁵)₂ oder Li ist; R¹³ und R¹⁴, jeweils gleich oder verschieden, ein Wasserstoffatom, eine Alkylgruppe sind oder unter Bildung eine Ethylengruppe oder einer 1,2-Dimethylethylengruppe kombiniert sind; R¹⁵ eine Alkylgruppe ist und X ein Chloratom, ein Bromatom oder ein Iodatom ist, unter Erhalt einer Verbindung der Formel (7), (8), (9) oder (10) Ar¹-(Ar²)m² (7)
  
  worin Ar¹, Ar², R¹⁰, R¹¹, R¹², R¹⁰¹, R¹¹¹ und R¹²¹ wie oben definiert sind und m² eine ganze Zahl von 1 bis 4 ist, umfaßt;
• 7. ein oben in 4 oder 5 genanntes Herstellungsverfahren, welches das Umsetzen einer Verbindung der nachstehenden Formel (3) oder (4), Ar¹(X¹)m¹ (3)
  
  wobei in Formel (3) Ar¹ eine Arylgruppe, die substituiert sein kann, oder eine Heteroarylgruppe, die substituiert sein kann, ist; X¹ ein Chloratom, ein Bromatom, ein Iodatom, eine Trifluormethansulfonyloxygruppe, eine Methansulfonyloxygruppe oder eine para-Toluolsulfonyloxygruppe ist und m¹ eine ganze Zahl von 1 bis 4 ist, und in Formel (4) R¹⁰¹, R¹¹¹ und R¹²¹, jeweils gleich oder verschieden, ein Wasserstoffatom, eine Alkylgruppe, eine Arylgruppe, die substituiert sein kann, eine Heteroarylgruppe, die substituiert sein kann, eine Alkoxycarbonylgruppe oder eine Cyanogruppe sind; X¹¹ ein Chloratom, ein Bromatom, ein Iodatom, eine Trifluormethansulfonyloxygruppe, eine Methansulfonyloxygruppe oder eine para-Toluolsulfonyloxygruppe ist, mit einer Sauerstoffverbindung oder einer Stickstoffverbindung der nachstehenden Formel (11) R¹⁶-QH (11)worin R¹⁶ eine Alkylgruppe, eine Arylgruppe, die substituiert sein kann, oder eine Heteroarylgruppe, die substituiert sein kann, ist; Q ein Sauerstoffatom,
  
  ist, worin R¹⁷, R¹⁸ und R¹⁹ ein Wasserstoffatom, eine Alkylgruppe, eine Arylgruppe, die substituiert sein kann, oder eine Heteroarylgruppe, die substituiert sein kann, sind; und R¹⁶ und R¹⁷ unter Bildung eines zweiwertigen aromatischen Ringes, der substituiert sein kann, kombiniert werden können, unter Erhalt einer Verbindung der nachstehenden Formel (12) oder (13) Ar¹(QR¹⁶)m³ (12)
  
  worin Ar¹, Q, R¹⁶, R¹⁰¹, R¹¹¹ und R¹²¹ wie oben definiert sind und m³ eine ganze Zahl von 1 bis 4 ist, umfaßt;
• 8. das oben in 4 oder 5 genannte Herstellungsverfahren, welches das Umsetzen einer aromatischen Verbindung der Formel (3) Ar¹(X¹)m¹ (3)worin Ar¹ eine Arylgruppe, die substituiert sein kann, oder eine Heteroarylgruppe, die substituiert sein kann, ist; X¹ ein Chloratom, ein Bromatom, ein Iodatom, eine Trifluormethansulfonyloxygruppe, eine Methansulfonyloxygruppe oder eine para-Toluolsulfonyloxygruppe ist, und m¹ eine ganze Zahl von 1 bis 4 ist, mit einer Carbonylverbindung oder einer Cyanoverbindung der Formel (14) R¹⁸-CH₂-R¹⁹ (14)worin R¹⁸ ein Wasserstoffatom, CO₂R²⁰, C(=O)R²¹ oder eine Cyanogruppe ist; R¹⁹ CO₂R²², C(=O)R²³ oder eine Cyanogruppe ist; R²⁰, R²¹, R²² und R²³ jeweils eine Alkylgruppe, eine Arylgruppe, die substituiert sein kann, oder eine Heteroarylgruppe, die substituiert sein kann, sind, unter Erhalt einer Verbindung der Formel (15)
  
  worin Ar¹, R¹⁸ und R¹⁹ wie oben definiert sind und m⁴ eine ganze Zahl von 1 bis 4 ist, umfaßt;
• 9. das oben in 4 oder 5 genannte Herstellungsverfahren, welches das Umsetzen einer aromatischen Verbindung der Formel (3) Ar¹(X¹)m¹ (3),worin Ar¹ eine Arylgruppe, die substituiert sein kann, oder eine Heteroarylgruppe, die substituiert sein kann, ist; X¹ ein Chloratom, ein Bromatom, ein Iodatom, eine Trifluormethansulfonyloxygruppe, eine Methansulfonyloxygruppe oder eine para-Toluolsulfonyloxygruppe ist und m¹ eine ganze Zahl von 1 bis 4 ist, mit Kohlenmonoxid und einem Alkohol der Formel (16) R²⁴OH (16),worin R²⁴ eine Alkylgruppe ist, unter Erhalt eines Carbonsäureesters der Formel (17) Ar¹(CO₂R²⁴)m⁵ (17) worin Ar¹ und R²⁴ wie oben definiert sind und m⁵ eine ganze Zahl von 1 bis 4 ist, umfaßt;
• 10. das oben in einem von 4 bis 9 genannte Herstellungsverfahren von ungesättigten Verbindungen, welches die Durchführung der Umsetzung in Gegenwart einer Base umfaßt.

Accordingly, the present invention includes the following:

• 1. a phosphine compound of the formula (1),
  
  wherein R ^{1 is} a hydrogen atom, an alkyl group, a cycloalkyl group or a phenyl group which may be substituted; R ² and R ³ are the same or different, an alkyl group, a cycloalkyl group or a phenyl group which may be substituted; R ⁴ and R ⁵ , each same or different, are a hydrogen atom, an alkyl group, a cycloalkyl group or a phenyl group which may be substituted; R ⁶ , R ⁷ , R ⁸ and R ^{9 are} each the same or different, an alkyl group, a cycloalkyl group, a phenyl group which may be substituted, an alkoxyl group, a dialkylamino group, a halogen atom, a benzyl group, a naphthyl group or a halogenated alkyl group ; R ⁶ and R ⁷ or R ⁸ and R ^{9 may} each be combined to form a fused ring, a trimethylene group, a tetramethylene group or a methylenedioxy group; p, q, r and s are each an integer from 0 to 5; and p + q and r + s are each in the range of 0 to 5;
• 2. a palladium-phosphine complex which can be obtained by reacting the phosphine compound mentioned above in 1 with a palladium compound;
• 3. the palladium-phosphine complex mentioned above in 2, wherein the palladium compound is a palladium salt or a palladium complex, wherein the valence of palladium is 4, 2 or 0;
• 4. A production process of an unsaturated compound or an aromatic compound using the above-mentioned palladium-phosphine complexes in 2 or 3 as a catalyst;
• 5. A production process of an unsaturated compound or an aromatic compound using the phosphine compound mentioned above in 1 and a palladium compound;
• 6. The production process mentioned above in 4 or 5, which comprises reacting a compound of the following formula (3) or (4): Ar ¹ (X ¹ ) m ¹ (3)
  
  wherein in formula (3) Ar ^{1 is} an aryl group which may be substituted or a heteroaryl group which may be substituted; X ^{1 is} a chlorine atom, a bromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, a methanesulfonyloxy group or a para-toluenesulfonyloxy group, and m ^{1 is} an integer of 1 to 4, and in formula (4) R ¹⁰¹ , R ¹¹¹ and R ¹²¹ each the same or different, a hydrogen atom, an alkyl group, an aryl group which may be substituted, a heteroaryl group which may be substituted, an alkoxycarbonyl group or a cyano group; X ^{11 is} a chlorine atom, a bromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, a methanesulfonyloxy group or a para-toluenesulfonyloxy group, with a compound represented by the following formula (5) or (6) Ar ² X ² (5)
  
  wherein in formula (5) Ar ^{2 is} an aryl group which may be substituted or a heteroaryl group which may be substituted; X ² B (OR ¹³ ) (OR ¹⁴ ), Sn (R ¹⁵ ) ₃ , MgX, ZnX, Al (R ¹⁵ ) ₂ or Li, and in formula (6) R ¹⁰ , R ¹¹ and R ¹² , are the same or differently, a hydrogen atom, an alkyl group, an aryl group which may be substituted, a heteroaryl group which may be substituted, an alkoxycarbonyl group or a cyano group; R ¹⁰ and R ¹² can be combined to form a single bond which forms a triple bond together with the existing double bond; X ^{3 is} a hydrogen atom, B (OR ¹³ ) (OR ¹⁴ ), Sn (R ¹⁵ ) ₃ , MgX, ZnX, Al (R ¹⁵ ) ₂ or Li; R ¹³ and R ¹⁴ , each same or different, are a hydrogen atom, an alkyl group or combined to form an ethylene group or a 1,2-dimethylethylene group; R ^{15 is} an alkyl group and X is a chlorine atom, a bromine atom or an iodine atom to give a compound of the formula (7), (8), (9) or (10) Ar ¹ - (Ar ² ) m ² (7)
  
  wherein Ar ¹ , Ar ² , R ¹⁰ , R ¹¹ , R ¹² , R ¹⁰¹ , R ¹¹¹ and R ^{121 are} as defined above and m ^{2 is} an integer of 1 to 4;
• 7. A production method mentioned above in FIG. 4 or 5, which comprises reacting a compound represented by the following formula (3) or (4) Ar ¹ (X ¹ ) m ¹ (3)
  
  wherein in formula (3) Ar ^{1 represents} an aryl group which may be substituted or a heteroaryl group which may be substituted can be tuiert is; X ^{1 is} a chlorine atom, a bromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, a methanesulfonyloxy group or a para-toluenesulfonyloxy group, and m ^{1 is} an integer of 1 to 4, and in formula (4) R ¹⁰¹ , R ¹¹¹ and R ¹²¹ each the same or different, a hydrogen atom, an alkyl group, an aryl group which may be substituted, a heteroaryl group which may be substituted, an alkoxycarbonyl group or a cyano group; X ^{11 is} a chlorine atom, a bromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, a methanesulfonyloxy group or a para-toluenesulfonyloxy group, with an oxygen compound or a nitrogen compound represented by the following formula (11) R ¹⁶ -QH (11) wherein R ^{16 is} an alkyl group, an aryl group which may be substituted, or a heteroaryl group which may be substituted; Q is an oxygen atom,
  
  wherein R ¹⁷ , R ¹⁸ and R ^{19 are} a hydrogen atom, an alkyl group, an aryl group which may be substituted, or a heteroaryl group which may be substituted; and R ¹⁶ and R ¹⁷ may be combined to form a divalent aromatic ring which may be substituted to obtain a compound represented by the following formula (12) or (13) Ar ¹ (QR ¹⁶ ) m ³ (12)
  
  wherein Ar ¹ , Q, R ¹⁶ , R ¹⁰¹ , R ¹¹¹ and R ^{121 are} as defined above and m ^{3 is} an integer of 1 to 4;
• 8. The production process mentioned above in 4 or 5, which comprises reacting an aromatic compound of the formula (3) Ar ¹ (X ¹ ) m ¹ (3) wherein Ar ^{1 is} an aryl group which may be substituted or a heteroaryl group which may be substituted; X ^{1 is} a chlorine atom, a bromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, a methanesulfonyloxy group or a para-toluenesulfonyloxy group, and m ^{1 is} an integer of 1 to 4, with a carbonyl compound or a cyano compound of the formula (14) R ¹⁸ -CH ₂ -R ¹⁹ (14) wherein R ^{18 is} a hydrogen atom, CO ₂ R ²⁰ , C (= O) R ²¹ or a cyano group; R ^{19 is} CO ₂ R ²² , C (= O) R ²³ or a cyano group; R ²⁰ , R ²¹ , R ²² and R ^{23 are} each an alkyl group, an aryl group which may be substituted, or a heteroaryl group which may be substituted to give a compound of the formula (15)
  
  wherein Ar ¹ , R ¹⁸ and R ^{19 are} as defined above and m ^{4 is} an integer of 1 to 4;
• 9. The production process mentioned above in 4 or 5, which comprises reacting an aromatic compound of the formula (3) Ar ¹ (X ¹ ) m ¹ (3), wherein Ar ^{1 is} an aryl group which may be substituted or a heteroaryl group which may be substituted; X ^{1 is} a chlorine atom, a bromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, a methanesulfonyloxy group or a para-toluenesulfonyloxy group, and m ^{1 is} an integer of 1 to 4, with carbon monoxide and an alcohol of the formula (16) R ²⁴ OH (16), wherein R ^{24 is} an alkyl group to obtain a carboxylic acid ester of the formula (17) Ar ¹ (CO ₂ R ²⁴ ) m ⁵ (17) wherein Ar ¹ and R ^{24 are} as defined above and m ^{5 is} an integer of 1 to 4;
• 10. The production process of unsaturated compounds mentioned above in any one of 4 to 9, which comprises carrying out the reaction in the presence of a base.

In of the present invention is linear under an alkyl group or branched alkyl group having 1 to 30 carbon atoms, or stronger preferably one with 1 to 10 carbon atoms to understand. Specific Examples of such an alkyl group are methyl, ethyl, n-propyl, Isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, Neopentyl, tert-pentyl, n-hexyl, isohexyl, 2-ethylhexyl, n-heptyl, n-octyl, n-nonyl and n-decyl. These groups can be reacted with (a) cycloalkyl group (s), which will be mentioned below, be substituted.

In of the present invention is a cycloalkyl group under cycloalkyl group to understand with 5 to 8 carbon atoms. Special examples such a cycloalkyl group include cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. These cycloalkyl groups can be combined with those mentioned above Be substituted alkyl groups.

In In the present invention, an alkoxy group is a linear one or branched alkoxy group having 1 to 30 carbon atoms, or stronger preferably one with 1 to 10 carbon atoms to understand. Specific Examples of such an alkoxy group include methoxy, ethoxy, n-propoxy, Isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentyloxy, Isopentyloxy, neopentyloxy, n-hexyloxy, isohexyloxy, 2-ethylhexyloxy, n-heptyloxy, n-octyloxy, n-nonyloxy and n-decyloxy.

In of the present invention is under an alkyl group of a dialkylamino group to understand an above-mentioned alkyl group, and the two alkyl groups can be the same or different. Examples of such a dialkylamino group include dimethylamino, diethylamino, di (n-propyl) amino, diisopropylamino, di (n-butyl) amino, Di (n-pentyl) amino and di (n-hexyl) amino.

In In the present invention, halogen atoms include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

In of the present invention is under a halogenated alkyl group to understand a group that is formed by one of the hydrogen atoms the above-mentioned alkyl groups by an above-mentioned halogen atom is replaced, wherein the most preferred halogen atom is a fluorine atom is. Specific examples of such halogenated alkyl groups include perfluoroalkyl groups such as trifluoromethyl, pentafluoroethyl, Heptafluoropropyl, etc. and fluoroalkyl such as difluoromethyl and monofluoromethyl etc.

In of the present invention is substituted by a phenyl group substituted may be a phenyl group in which at least one of the hydrogen atoms substituted on the phenyl group by (a) substituent, or an unsubstituted phenyl group. Examples of Substituents include an alkyl group, a cycloalkyl group, an alkoxyl group, a dialkylamino group, a halogen atom, a phenyl group, a benzyl group, a naphthyl group and a halogenated alkyl group, which are all mentioned above.

following is the description of the phosphine compounds of the present invention.

In the phosphine compounds of the formula (1) of the present invention, R ^{1 is} a hydrogen atom, an alkyl group, a cycloalkyl group or a phenyl group which may be substituted, and specific examples of such alkyl groups, cycloalkyl groups and phenyl groups which may be substituted include those mentioned above;
R ² and R ³ , each same or different, are an alkyl group, a cycloalkyl group or a phenyl group which may be substituted, and specific examples of such alkyl groups, cycloalkyl groups and phenyl groups which may be substituted include those mentioned above;
R ⁴ and R ⁵ , each same or different, are a hydrogen atom, an alkyl group, a cycloalkyl group or a phenyl group which may be substituted, and specific examples of such alkyl groups, cycloalkyl groups and phenyl groups which may be substituted include those mentioned above;
R ⁶ , R ⁷ , R ⁸ and R ^{9 are} each the same or different, a hydrogen atom, an alkyl group, a cycloalkyl group or a phenyl group which may be substituted, an alkoxyl group, a dialkylamino group, a halogen atom, a benzyl group, a naphthyl group and a halogenated alkyl group, and specific examples of such alkyl groups, cycloalkyl groups, phenyl groups which may be substituted, alkoxyl groups, dialkylamino groups, halogen atoms and halogenated alkyl groups include those mentioned above;
For example, R ⁶ and R ⁷ , R ⁸ and R ^{9 may} each be combined to form a fused ring, a trimethylene group, a tetramethylene group or a methylenedioxy group. Examples of the fused ring include a naphthalene ring, an anthracene ring, a phenanthrene ring, a benzofuran ring, a benzothiophene ring, an indole ring and a quinoline ring obtained by condensing R ⁶ , R ⁷ , R ⁸ and R ⁹ with the phenyl group on which they are present. be formed.

worin Hal Chlor oder Brom ist und Ph Phenyl ist.Specifically, the phosphine compounds of the formula (1) of the present invention can be produced, for example, by the method shown below, but the present invention is not limited by this method.

wherein Hal is chlorine or bromine and Ph is phenyl.

A the phosphine compounds of the present invention, 2,2-diphenyl-1- (diphenylphosphino) -1-methylcyclopropane, can be prepared by the monobromocyclopropane compound (C) or the monochlorocyclopropane compound (C) with magnesium metal to give a cyclopropylmagnesium halide and then the latter compound with diphenylphosphine chloride in Presence of copper iodide is reacted. The monobromocyclopropane compound (C) can in turn be prepared by the reaction of the dibromocyclopropane compound (B) obtained by the reaction of 1,1-diphenylethylene (A) with potassium tert-butoxide and bromoform available is enabled with n-butyl lithium and methyl iodide. Alternatively it will 1,1-diphenylethylene with 1,1-dichloroethane and n-butyllithium below Obtained the Monochlorcyclopropanverbindung (C) reacted.

Diarylmonohalogencyclopropanverbindungen (C), the intermediates for the phosphine compounds of the present invention in the above shown methods are useful Intermediates for the preparation of the phosphine compounds of the present invention. Namely, the phosphine compounds of the present invention usually become prepared by these Diarylmonohalogencyclopropanverbindungen (C) with lithium metal, alkyl lithium or magnesium metal to obtain of cyclopropyllithium derivatives or cyclopropylmagnesium halide derivatives which are then reacted with different Chlorphosphinderivaten be implemented.

following is the more detailed Description of the preparation processes of the phosphine compounds of present invention and the monohalocyclopropane intermediates.

In the process for producing the above-mentioned phosphine compounds of the present invention the diaryldihalocyclopropanes (B) are obtained by reacting the diarylethylenes (A) are reacted with halogenoforms in the presence of bases.

The amount used in the halogen form is preferably, with respect to moles about 0.1 to 10 times or more preferably about 0.5 times up to 4 times the amount of diarylethylene (A).

Specific Examples of the reaction solvent include hydrocarbons such as pentane, hexane, heptane, etc .; aromatic Hydrocarbons such as benzene, toluene, xylene, etc .; and ethers, such as diethyl ether, tetrahydrofuran, dioxane, etc. Among them preferably hydrocarbons, such as pentane, hexane, heptane, etc. used. The amount of solvent used is, with respect to to the volume, about 0.2 to 30 times or more preferably about 0.5 to 10 times the amount of the diarylethylene (A).

The Reaction becomes ordinary in an atmosphere from inert gases such as nitrogen, argon, etc. performed. The Reaction time is usually 10 minutes to about 30 hours, or more preferably 30 minutes to about 16 hours. The reaction is usually carried out at temperatures from -80 to about 100 ° C, or stronger preferably -20 up to about 60 ° C, completed although these reaction conditions depend on the type and quantities of the used diarylethylene (A) and the halogenoform used changed accordingly can be.

To Completion of the reaction, the reaction mixture is worked up as usual, whereby the target compound is obtained.

In the method shown above the diarylmonohalocyclopropanes (C) are obtained by the Diaryldihalocyclopropanes (B) with halides or dialkyl sulfate in the presence of an organometallic compound such as an organolithium compound be implemented.

Specific Examples of the organolithium compound include methyllithium, ethyllithium, n-propyllithium, n-butyllithium, sec-butyllithium, tert-butyllithium and phenyllithium. Among these are n-butyllithium, sec-butyllithium and tert-butyllithium stronger preferably used. The amount of organolithium compound used is, in terms of mol, preferably about 0.4 to 3.0 times, and especially preferably about 0.8 to 1.5 times the amount of the diaryldihalocyclopropane used (B).

Specific Examples of this reaction solvent include ethers such as diethyl ether, tetrahydrofuran, dioxane, diisopropyl ether, Dimethoxyethane, etc., wherein diethyl ether and tetrahydrofuran more preferred be used. The amount of the solvent used is, in terms of to the volume, preferably about 1.0 to 50 times, or especially preferably about 2.0 to 25 times the amount of diarylethylene used (A).

The Reaction becomes ordinary in an atmosphere from inert gases such as nitrogen, argon, etc., and the reaction time is usually 10 minutes to about 40 hours, or more preferably 30 minutes to about 18 hours, and the reaction temperature is usually -120 to about 100 ° C, or stronger preferably -80 up to about 60 ° C, although these reaction conditions depend on the type and amount the Diaryldihalogencyclopropane used (B) and halides accordingly changed can be.

To completion of the reaction, the reaction mixture is worked up as usual, whereby the target compound is obtained.

moreover can the diaryl monohalocyclopropanes (C) in the process shown above can be obtained by the diarylethylenes (A) with dihalides (For example, 1,1-dichloroethane and 1,1-dibromoethane) in the presence an organometallic compound such as an organolithium compound, etc. be implemented.

Specific Examples of the organolithium compounds include methyllithium, Ethyllithium, n-propyllithium, n-butyllithium, sec-butyllithium, tert-butyllithium and phenyllithium. Among these are n-butyllithium, sec-butyllithium and tert-butyllithium stronger preferably used. And the amount of organolithium compound used is, in terms of mol, preferably about 0.4 to 20 times and especially preferably about 0.8 to 10 times the amount of the diarylethylene compound used (A).

Specific Examples of the reaction solvent include ethers such as diethyl ether, tetrahydrofuran, dioxane, diisopropyl ether and dimethoxyethane, among which diethyl ether and tetrahydrofuran stronger preferably used. The amount of solvent used is, in terms of volume, about 1.0 to 50 times and especially preferably about 2.0 to 25 times the amount of diarylethylene used (A).

The Reaction becomes ordinary in an atmosphere from inert gases such as nitrogen, argon, etc., and the reaction time is usually 10 minutes to about 40 hours, or more preferably 30 minutes to about 18 hours, and the reaction temperature is usually -120 to about 120 ° C, or stronger preferably -80 up to about 60 ° C, although these reaction conditions depend on the type and amount the diaryldihalocyclopropanes (B) and dihalides used changed accordingly can be.

To completion of the reaction, the reaction mixture is worked up as usual, whereby the target compound is obtained.

The Phosphine compounds (D) of the present invention are prepared according to the above obtained by the Diarylmonohalogencyclopropane (C) with metal such as lithium and magnesium to give cyclopropyllithium compounds or Cyclopropylmagnesiumhalogeniden be followed by the reaction of these organometallic compounds with chlorophosphines.

Specific Examples of the metal that can be used include lithium and magnesium. In cases, where lithium is used is the amount of lithium used, with respect to moles, preferably about 1.0 to 3.0 times, or more preferably about 1.5 times to 2.5 times the amount of substrate used, the diaryl monohalocyclopropanes (C).

And in cases, where magnesium is used, the amount of used is Magnesium, in terms of mol, preferably about 1.0 to 3.0 times or more preferably about 1.2 to 1.5 times the amount of used substrate, the Diarylmonohalogencyclopropane (C).

Specific Examples of the reaction solvent include ethers such as diethyl ether, tetrahydrofuran, dioxane, diisopropyl ether and dimethoxyethane, among which diethyl ether and tetrahydrofuran stronger preferably used. The amount of solvent used is, in volume, preferably about 1.0 to 50 times and more preferably about 2.0 to 25 times the amount of used diaryl monohalocyclopropanes (C).

The Reaction becomes ordinary in an atmosphere from inert gases such as nitrogen, argon, etc. performed. The Reaction time is usually 10 minutes to about 40 hours, or more preferably 30 minutes to about 18 hours, and the reaction temperature is usually -120 to about 120 ° C, or stronger preferably -80 up to about 80 ° C, although these reaction conditions depend on the type and amount of used diaryl monohalocyclopropanes (C) and chlorophosphines changed accordingly can be.

To completion of the reaction, the reaction mixture is worked up as usual, whereby the target compound is obtained.

The thus obtained phosphine compounds of the formula (1) of the present invention Invention form as ligands palladium-phosphine complexes with palladium compounds.

The Palladium-phosphine complexes formed by the reaction of phosphine compounds of the formula (1) of the present invention with palladium compounds available are, can be prepared by the phosphine compounds of the present Invention with π-allylpalladium chloride dimer (II) or reacted with tris (dibenzylidene) dipalladium (0) according to the methods, which are described in the literature: for example, Y. Uozumi and T. Hayashi, J. Am. Chem. Soc., (1991), Vol. 113, 9887; Gregory C. Fu, et al., J. Am. Chem. Soc., (2001), Vol. 123, 2719.

Specific examples of the palladium compounds which can be used include palladium (IV) compounds such as sodium hexachloropalladate (IV) tetrahydrate, potassium hexachloropalladate (IV), etc., palladium (II) compounds such as palladium chloride (II), palladium bromide (II), Palladium acetate (II), palladium (II) acetylacetonate, dichlorobis (benzonitrile) palladium (II), dichlorobis (acetonitrile) palladium (II), dichlorotetramminepalladium (II), Dichloro (cycloocta-1,5-diene) palladium (II), palladium trifluoroacetate (II) and π-allylpalladium chloride dimer, etc. and palladium (0) compounds such as tris (dibenzylideneacetone) dipalladium (0), tris (dibenzylideneacetone) dipalladium chloroform adduct (0), etc. Among them, dichlorobis (benzonitrile) palladium (II), π-allylpalladium chloride dimer (II), tris (dibenzylideneacetone) dipalladium (0) and tris (dibenzylideneacetone) dipalladium chloroform adduct (0) are more preferably used. The amount of the palladium compound used, in terms of mol, is preferably about 0.1 to 8.0 times, and more preferably about 0.2 to 4.0 times, the amount of the phosphine compound used.

The Reaction solvent is not limited to a particular, but it can be any solvent used as long as it does not seriously hinder the reaction. Examples of such solvents include aliphatic organic solvents such as pentane, hexane, heptane, octane, etc .; alicyclic organic solvent such as cyclohexane, methylcyclohexane, etc .; aromatic organic solvents such as benzene, toluene, xylene, etc .; Ethers, such as diethyl ether, diisopropyl ether, Dimethoxyethane, tetrahydrofuran, dioxane, dioxolane, etc .; acetonitrile; dimethylformamide; Dimethylsulfoxide and hexamethylphosphoric triamide.

Under these are aromatic organic solvents such as benzene, toluene, Xylene, etc. and ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, Dioxane, etc. stronger preferably used. The amount of the solvent used is, in terms of to the volume, preferably about 1.0 to 50 times and especially preferably about 2.0 to 25 times the amount of the phosphine compound used.

The Reaction becomes ordinary in an atmosphere from inert gases such as nitrogen, argon, etc. performed. The Reaction time is usually 10 minutes to about 40 hours, or more preferably 30 minutes to about 18 hours, and the reaction temperature is usually -20 to about 160 ° C, or stronger preferably 0 to about 120 ° C, although these reaction conditions depend on the type and amount of used phosphine compounds and the palladium compounds used changed accordingly can be.

To completion of the reaction, the reaction mixture is worked up as usual, whereby the target compound is obtained.

The Palladium-phosphine complexes formed by reacting the phosphine compounds obtainable with palladium compounds of the present invention, can as catalysts in carbon-carbon bond formation reactions in compounds with unsaturated Bonds (for example, Suzuki coupling reaction, Stille coupling reaction, Negishi coupling reaction, Sonogashira coupling reaction, α-arylation carbonyl compounds, alkoxycarbonylation, etc.), carbon-nitrogen bond formation reactions (for example, arylamination reaction, vinylamine reaction, etc.) and carbon-oxygen bond formation reactions (for example, aryl etherification reaction, vinyl etherification reaction, etc.).

According to the present Invention may be unsaturated Compound or an aromatic compound advantageously by the use of the palladium-phosphine complex or alternatively by the use of the phosphine compound and the palladium compound be generated.

One of the production methods of the present invention is selected from the following reactions:

(Hetero) aryl compounds of the formula (3) used in the present invention can, include (hetero) aryl bromides, (hetero) aryl chlorides, (hetero) aryl iodides, (Hetero) aryl trifluoromethanesulfonates, (hetero) aryl methanesulfonates, (Hetero) aryl-para-toluenesulfonates and (hetero) aryl compounds with 1-4 halogen atoms or sulfonate components.

Specific Examples of the (hetero) aryl compounds include aryl bromides such as Bromobenzene, 1,4-dibromobenzene, 1,3,5-tribromobenzene, p-bromoanisole, p-bromotoluene, o-bromophenol, p-bromophenol, 2-bromobenzotrifluoride, 4-bromobenzotrifluoride, mesityl bromide, 4-bromophenethyl alcohol, 2-bromo-m-xylene, 2-bromo-p-xylene, 5-bromo-m-xylene, 1-bromo-4- (trifluoromethoxy) benzene, 2-bromobiphenyl, 4-bromobiphenyl, 4-bromo-1,2- (methylenedioxy) benzene, 1-bromonaphthalene, 2-bromonaphthalene, 1-bromo-2-methylnaphthalene, 1-bromo-4-methylnaphthalene, 1,4-dibromonaphthalene, 4,4'-dibromobiphenyl, 2-bromothiophene, 2-bromopyridine, 9-bromophenanthrene, 2-bromofuran, 2,4-difluorobromobenzene, 2,4-di (trifluoromethyl) bromobenzene, 4-bromodimethylaminobenzene, 4-bromobenzonitrile, Tetrabromoperylene, dibromoanthanthrone, etc .; and the connections, which are formed by the bromine atom (s) in the above Aryl bromides are replaced by (a) chlorine or iodine atom (s).

Examples The sulfonates include the compounds that are formed by the bromine atom in the above-mentioned bromide by either a trifluoromethanesulfonyloxy group, a methanesulfonyloxy group or a para-toluenesulfonyloxy group is replaced. These sulfonates can readily by the treatment of precursor phenols with sulfonylating agents such as trifluoromethanesulfonic anhydride, methanesulfonyl chloride, etc. in the presence of bases such as triethylamine, etc.

The unsaturated compounds represented by the formula (4) in the present invention include the compounds having a double bond between a carbon atom bearing a substituent X ¹¹ serving as a leaving group in the reaction and a carbon atom adjacent thereto such as vinyl halides, vinyl sulfonates and their analogs. Typical examples of the bromides such as vinyl halides and their analogs include bromoethylene, 1-bromopropene, 2-bromopropene, 2-bromo-2-butene, 1-bromo-1-butene, 1-bromo-2-butene, bromocyclopentene, bromocyclohexene, α- Bromostyrene, β-bromostyrene, 2,2-diphenyl-1-bromoethylene, 1,2-diphenylbromethylene, 3-bromo-2-propen-1-ol, 2-bromo-2-propen-1-ol, methyl-2- bromacrylate and 2-bromoacrylonitrile.

Examples of the sulfonates and their analogs include trifluoromethanesulfonates as a member, trifluoromethanesulfonyloxyethylene, 1-trifluoromethanesulfonyloxy-propene, 2-trifluoromethanesulfonyloxy-propene, trifluoromethanesulfonyloxycyclopentene, trifluoromethanesulfonyloxycyclohexene and 1-trifluoromethanesulfonylo xy-1-methoxyethylene.

(Hetero) aryl compounds of the formula (5) used in the present invention can, include boronic acids, Boronsäureester, Trialkylaryl tin compounds, aryl magnesium halides, aryl zinc halides, Dialkylarylaluminium compounds and aryllithium compounds.

Even though there is no special restriction with respect to the boronic acids Examples of boronic acids include boronic acids such as phenylboronic acid, 4-methylphenylboronic acid, 2-thienylboronic acid, 2-furylboronic acid, 2-pyridylboronic acid, 2,3,4,5,6-pentafluorophenylboronic acid, 2-fluorophenylboronic acid, 4-chlorophenylboronic acid, 2-bromophenylboronic acid, 4-iodophenylboronic acid, 2,4-difluorophenylboronic acid, 4-trifluoromethylphenylboronic acid, 3-cyanophenylboronic acid, 4-formylphenylboronic acid, 4-methoxyphenylboronic acid, 1-naphthylboronic acid, ferrocenylboronic acid, 4-hydroxyphenylboronic acid, etc. and esters (for example, dimethyl ester, diethyl ester, dipropyl ester and pinacol ester, etc.) of the above-mentioned arylboronic acids.

Even though there is no special restriction with respect to the trialkyltin compounds, examples include the trialkyltin compounds phenyltrimethyltin, phenyltriethyltin, Phenyltributyltin, 2-methylphenyltributyltin, 2,4,6-trimethylphenyltributyltin, 4-methoxyphenyltributyltin, 2-pyridyltributyltin, 3-pyridyltributyltin, 2-thienyltributyltin, 3-thienyltributyltin and 2-furyltributyltin.

Even though there is no special restriction with respect to the arylmagnesium halides, arylzinc halides, dialkylarylaluminum compounds and aryllithium compounds, examples of the compounds are, for example Phenylmagnesium halide, 4-biphenylmagnesium halide, 2-biphenylmagnesium halide, 4-methoxyphenylmagnesium halide, 4-methylphenylmagnesium halide, 3-methoxyphenylmagnesium halide, 3-methylphenylmagnesium halide, 2-methoxyphenylmagnesium halide, 2-methylphenylmagnesium halide, 2-pyridylmagnesium halide, 2-thienylmagnesium halide, 2-furylmagnesium halide, Phenylzinc halide, 4-biphenylzinc halide, 2-biphenylzinc halide, 2-methylphenylzinc halide, 3-methylphenylzinc halide, 4-methylphenylzinc halide, 2,6-dimethylphenylzinc halide, 2,4,6-trimethylphenylzinc halides, 4-methoxyphenylzinc halides, 2-pyridylzinc halides, 3-pyridylzinc halides, 2-thienylzinc halides, 2-furylzinc halides, phenyldimethylaluminum, Phenyldiethylaluminum, phenyldipropylaluminum, phenyldiisopropylaluminum, Phenyldibutylaluminum, phenyldiisobutylaluminum, 2-methylphenyldiethylaluminum, 4-methoxyphenyldiethylaluminum, 2-thienyldiethylaluminum, phenyllithium, 2-methylphenyllithium, 4-methoxyphenyllithium, 2-thienyllithium, 2-pyridyllithium, 2-furyllithium, etc.

Unsaturated compounds of the formula (6) include olefins which may be substituted, terminal acetylene compounds, which can be substituted, acrylate and acrylonitriles attached to the α- or β-position can be substituted (Hetero) aryl compounds having a vinyl group and (a) may have further substituents, alkenylboronic, Alkenylboronsäureester, Trialkylalkenyltin compounds, alkenylmagnesium halides, alkenylzinc halides, Dialkylalkenylaluminiumverbindungen and Alkenyllithiumverbindungen.

Specific Examples of olefins that may be substituted include ethylene, propene, 1-butene, 2-butene, 1-heptene, 2-heptene, cyclopentene, cyclohexene, methylcyclohexene, Allyl alcohol, methacrylic alcohol, homoallyl alcohol, crotyl alcohol, Crotonaldehyde, vinyl butyl ether and allyl benzene.

Even though there is no special restriction with respect to the acrylic esters and acrylonitriles attached to the α- or β-position can be substituted Examples of such groups include methyl acrylate, ethyl acrylate, Butyl acrylate, tert-butyl acrylate, ethyl methacrylate, ethyl crotonate, Acrylonitrile, methacrylonitrile and crotononitrile.

Even though there is no special restriction with respect to the (hetero) aryl compounds which is a vinyl group and may have (a) further substituent (s) include Examples of such a group styrene, stilbene, 4-methylstyrene, 3-methylstyrene, 4-vinylmethoxybenzene, β-methoxystyrene, α-methylstyrene, 2-vinylthiophene, 3-vinylthiophene, 2-vinylpyridine and 2-vinylfuran.

Even though there is no special restriction with respect to the alkenylboronic acids Examples of such a group include boronic acids such as Vinyl boronic acid, 1-propen-1-ylboronic acid, 1-propen-2-ylboronic acid, 1-butene-1-ylboronic acid, 1-buten-2-ylboronic acid, 2-buten-2-ylboronic acid, 1-penten-1-ylboronic acid, α-styrylboronic acid, β-styrylboronic acid, 1,2-diphenylethenylboronic acid, 2,2-diphenylethenylboronic acid, cyclopentenylboronic acid, cyclohexenylboronic acid, 2-methylcyclohexenylboronic acid, etc. and their esters (for example dimethyl ester, diethyl ester, dipropyl ester, Pinacol ester, etc.) of these alkenylboronic acids.

Even though there is no special restriction with respect to the trialkylalkenyltin compounds Examples of such compounds vinyltrimethyltin, vinyltriethyltin, Vinyltripropyltin, vinyltributyltin, 1-propen-1-yltributyltin, 1-buten-1-yltributyltin, 1-ethoxyethenyltributyltin, α-styryltributyltin, β-styryltributyltin, 1,2-diphenylethenyltributyltin, 2,2-diphenylethenyltributyltin, Cyclopentenyltributyltin, cyclohexenyltributyltin.

Even though there is no special restriction with respect to the alkenylmagnesium halides, alkenylzinc halides, Dialkylalkenylaluminiumverbindungen and Alkenyllithiumverbindungen Examples of such groups include compounds such as vinylmagnesium halides, 1-propen-1-ylmagnesium halides, 1-propen-2-ylmagnesium halides, 1-buten-1-ylmagnesium halides, α-styrylmagnesium halides, β-styrylmagnesium halides, 1,2-diphenylethenylmagnesium halides, 2,2-diphenylethenylmagnesium halides, Cyclopentenylmagnesium halides, cyclohexenylmagnesium halides, Vinylzinc halides, 1-propen-1-ylzinc halides, 1-propen-2-ylzinc halides, 1-buten-1-ylzinc halides, α-styrylzinc halides, β-styrylzinc halides, 1,2-diphenylethenylmagnesium halides, 2,2-diphenylethenylmagnesium halides, Cyclopentenylzinc halides, cyclohexenylzinc halides, vinyldimethylaluminum, Vinyldiethylaluminum, vinyldipropylaluminum, vinyldiisopropylaluminum, Vinyldibutylaluminum, vinyldiisobutylaluminum, 1-propen-1-yl-diethylaluminum, β-styryldiethylaluminum, Vinyl lithium, 1-propene-1-yl lithium, β-styryllithium, cyclopentenyllithium, Cyclohexenyllithium, etc.

Even though there is no special restriction with respect to the terminal acetylenic compounds substituted could be, Examples of such compounds include acetylene, propyne, 1-butyne, 1-pentyne, 1-hexyne, 1-heptine, 1-octyne, phenylacetylene, 2-propyn-1-ol, 3-butyn-1-ol, 2-methyl-3-butyn-2-ol, 1-ethynylcyclohexanol and trimethylsilylacetylene.

at This manufacturing process, it is only necessary that not less than 1 mole of boronic acids, Trialkylaryltin compounds, arylmagnesium halides, arylzinc halides, Dialkylarylaluminium compounds and aryllithium compounds in the reaction system per 1 mole of the aromatic compound (3) or the unsaturated one Compound (4) exists. Stronger preferably, these compounds existed in the reaction system, in terms of moles, but in the 1- to 10-fold amount of the amount the aromatic compound (3) or the unsaturated compound (4), since the recovery unreacted materials: boronic acids, trialkylaryl tin compounds, Arylmagnesium halides, arylzinc halides, dialkylarylaluminum compounds and aryllithium compounds, becomes problematic.

at This manufacturing process, it is only necessary that not less than 1 mole of the terminal acetylenic compounds substituted could be, the acrylic acid ester, which at the α- or β-position can be substituted and the (hetero) aryl compounds and acrylonitriles having a vinyl group and have (a) further substituents, in the reaction system per 1 mole of the aromatic compound (3) or the unsaturated one Compound (4) exists. However, it is more preferable that these Compounds in the reaction system, in terms of moles, in the 1- to 10 times the amount of the aromatic compound (3) or the unsaturated one Compound (4) exist because the recovery of unreacted Materials comprising terminal acetylenic compounds substituted could be, acrylate, which at the α- or β-position can be substituted and (hetero) aryl compounds and acrylonitriles having a vinyl group and (a) other substituent (s) will be problematic.

at This preparation method suitably bases as auxiliaries used. The bases to be used may be inorganic and / or selected organic bases be without them specifically on the listed limited are. Examples of such bases are carbonates of alkali metals or alkaline earth metals, such as lithium carbonate, sodium carbonate, potassium carbonate, Rubidium carbonate, cesium carbonate, magnesium carbonate, calcium carbonate, Barium carbonate, etc .; Alkali metal alkoxides, such as sodium methoxide, sodium ethoxide, Sodium phenoxide, sodium tert-butoxide, potassium methoxide, potassium ethoxide, Potassium phenoxide, potassium tert-butoxide, lithium methoxide, lithium ethoxide, Lithium phenoxide, lithium tert-butoxide, etc .; Hydroxides of alkali metals or alkaline earth metals, such as sodium hydroxide, potassium hydroxide, lithium hydroxide, Barium hydroxide, etc .; Phosphates of alkali metals, such as lithium phosphate, Potassium phosphate, sodium phosphate, etc .; Amines, such as trimethylamine, Triethylamine, triisopropylamine, tricyclohexylamine, diethylamine, Diisopropylamine, methylmorpholine, pyridine and picoline; and alkali metal fluorides, such as lithium fluoride, potassium fluoride, sodium fluoride, cesium fluoride, Rubidium fluoride, etc.

The amount of the base used is preferably not less than 1 mole per 1 mole of the aromatic compound (3) or the unsaturated compound (4). With less than 1 mole equivalent of the base, the yield of the unsaturated compound obtained by the method of the present invention can be reduced. be reduced. However, even the addition of a large excess of the base hardly adversely affects the yield of the obtained unsaturated compound, but it makes the work-up procedure after completion of the reaction problematic. Therefore, the amount of the base used, in terms of mol, is more preferably in the range of 1 to 5 times.

The Procedure above for the production of unsaturated Compounds are usually called in the presence of a solvent carried out, that for the reactions are inert. The solvents, which can be used are not limited to special, however, as long as they do not seriously hamper the reactions, they include aliphatic organic solvents, such as pentane, hexane, heptane, octane, etc .; alicyclic organic Solvent, such as cyclohexane, methylcyclohexane, etc .; aromatic organic solvents, such as benzene, toluene, xylene, etc .; Ethers, such as diethyl ether, diisopropyl ether, Dimethoxyethane, tetrahydrofuran, dioxane, dioxolane, etc .; acetonitrile; dimethylformamide; dimethyl sulfoxide; Hexamethylphosphoric triamide, etc. Among these solvents become aromatic, organic solvents, such as benzene, toluene, xylene, etc., and ethers, such as diethyl ether, dimethoxyethane, Tetrahydrofuran, dioxane, etc., more preferably used.

The The present invention can be carried out in an atmosphere of inert gases, such as nitrogen, Argon, etc., be carried out under atmospheric pressure or under elevated pressure.

The The present invention can be carried out at temperatures in the range of about 0 ° C to 300 ° C, or more preferred be carried out at temperatures in the range of about 20 ° C to 200 ° C.

The Reaction time of the present invention varies depending on the nature of the reaction and the reaction temperature, however, may be off ranging from about several minutes to 72 hours.

To Termination of the reaction, the reaction mixture by conventional Treated method, whereby the target compound is obtained.

Another production method of the present invention is one selected from the following reactions:

consequently becomes an aromatic compound (3) or an unsaturated compound (4) with an oxygen or nitrogen compound (11) in the presence a base reacted by the palladium-phosphine complex of the present Invention is used as a catalyst or by the palladium compound and phosphine compound of the present invention as a catalyst be used, whereby a compound (12): an aromatic Ether or an aromatic nitrogen compound, and a compound (13): an alkenyl ether or alkenyl nitrogen compound become.

Examples the (hetero) aryl compound represented by formula (3) and the unsaturated compounds represented by formula (4), which are described in used in the present invention include the same like the above.

Examples of the oxygen compound of the formula (II) used in the present invention include alcohols which may be substituted, phenols which may be substituted, and heterocyclic compounds which have hydroxyl group (s) and may be further substituted, and examples The nitrogen compound of the formula (II) used in the present invention includes primary amines, secondary amines, amides, imines, (di) alkylamines which may be substituted, (di) arylalkylamines which may be substituted, (di) heteroarylamines which may be substituted, alkylarylamines which may be substituted, alkylheteroarylamines which may be substituted , and amides and imines, which may be substituted.

Specific Examples of the oxygen compound include the following: namely phenol, 2-methoxyphenol, 2-tert-butylphenol, 2-methylphenol, 2-dimethylaminophenol, 3-methoxyphenol, 3-tert-butylphenol, 3-methylphenol, 3-dimethylaminophenol, 4-methoxyphenol, 4-tert-butylphenol, 4-methylphenol, 4-dimethylaminophenol, 1-naphthol, 2-biphenol, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol and tert-butanol, although not on the listed limited are.

Even though Specific examples of the nitrogen compounds shown below are not limited to these. For primary amines serve aliphatic primary Amines, such as ethylamine, propylamine, butylamine, isobutylamine, tert-butylamine, Pentylamine, cyclopentylamine, hexylamine, cyclohexylamine, heptylamine, Octylamine, etc., and aromatic primary amines such as aniline, m-fluoroaniline, p-fluoranlin, o-anisidine, m-anisidine, o-toluidine, m-toluidine, p-toluidine, 2-naphthylamine, 2-aminobiphenyl, 4-aminobiphenyl, 3,4-methylenedioxyaniline, m-xylidine, p-xylidine, m-phenylenediamine, etc., as examples.

Even though there is no special restriction with respect to the secondary Amines, these include, for example, cyclic secondary amines such as piperazine, 2-methylpiperazine, homopiperazine, N-methylhomopiperazine, 2,6-dimethylpiperazine, N-methylpiperazine, N-ethylpiperazine, N-ethoxycarbonylpiperazine, N-benzylpiperazine, morpholine, 2,6-dimethylmorpholine, piperidine, 2,6-dimethylpiperidine, 3,3-dimethylpiperidine, 3,5-dimethylpiperidine, 2-ethylpiperidine, 4-piperidone, pyrrolidine, 2,5-dimethylpyrrolidine, Carbazole, indole, indoline, acridone, quinacridone, etc., and acyclic secondary Amines such as dimethylamine, diethylamine and N-methylaniline, N-ethylaniline, N-methylbenzylamine, N-methylphenethylamine and diphenylamine derivatives, which may be further substituted on the aromatic ring.

Even though there is no special restriction with respect to the imines, these include, for example, benzophenone imine, 4,4'-Dimethoxybenzophenonimin, etc.

Even though there is no special restriction with respect to the amides, these include, for example, 2-azetidinone (β-propiolactam), γ-butyrolactam, δ-valerolactam, ε-caprolactam, Acetamide, propionamide, cyclohexylcarboxamide, benzamide, N-methylformamide, N-methylacetamide, N-ethylacetamide, N-methylcyclohexylcarboxamide, N-methylbenzamide, etc.

at This manufacturing process should use the oxygen or nitrogen compound (11) in the reaction system in the range of not less than 1 mol per 1 mole of the aromatic compound (3) or the unsaturated one Compound (4) are present. However, it is more preferred that the oxygen or nitrogen compound in the reaction system in the range of 1 to 2 mol per 1 mol of the aromatic compound (3) or the unsaturated one Compound (4) is present since the recovery of unreacted Oxygen or nitrogen compound (11) is problematic.

at The production method of the present invention is preferably Bases used as adjuncts. Such bases to be used may be inorganic bases and / or organic bases and are not limited to special ones. Consequently, examples include the bases used are preferably carbonates of alkali metals or alkaline earth metals, such as lithium carbonate, sodium carbonate, potassium carbonate, Rubidium carbonate, cesium carbonate, magnesium carbonate, calcium carbonate, Barium carbonate, etc .; Alkoxides of alkali metals, such as sodium methoxide, Sodium ethoxide, sodium phenoxide, sodium tert-butoxide, potassium methoxide, Potassium ethoxide, potassium phenoxide, potassium tert-butoxide, lithium methoxide, lithium ethoxide, Lithium phenoxide, lithium tert-butoxide, etc .; Phosphates of alkali metals, such as lithium phosphate, potassium phosphate, sodium phosphate, etc.

The Amount of base used is preferably not less than 1 mole per 1 mole of the aromatic Compound (3) or the unsaturated Compound (4). At less than 1 mol of the base, the yield the unsaturated one Compound obtained by the method of the present invention will be reduced. Nevertheless, even the addition of one affects big surplus the base hardly adversely affects the yield of the unsaturated Compound produced by the manufacturing process of the present Invention available is, but makes the refurbishment process after completion the reaction problematic.

consequently the amount of base used, with respect to moles, is preferably in the range of 1 to 5 times the amount of the aromatic compound (3) or the unsaturated one Compound (4).

The The above production method of the unsaturated compounds is usually referred to in a solvent, that for the reaction is inert, carried out. Nevertheless, every solvent can without a special restriction used as long as it does not seriously hinder the reaction. Examples of such preferred solvents include aliphatic ones organic solvents, such as pentane, hexane, heptane, octane, etc .; alicyclic organic Solvent, such as cyclohexane, methylcyclohexane, etc .; aromatic organic solvents, such as benzene, toluene, xylene, etc .; Ethers, such as diethyl ether, diisopropyl ether, Dimethoxyethane, tetrahydrofuran, dioxane, dioxolane, etc .; acetonitrile, Dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide. Under these are aromatic organic solvents, such as benzene, toluene, Xylene, etc., and ethers, such as diethyl ether, dimethoxyethane, tetrahydrofuran, Dioxane, etc., stronger preferably used.

The The present invention can be carried out in an atmosphere of inert gases, such as nitrogen, Argon, etc. are carried out under normal pressure or under elevated pressure.

The The present invention can be carried out at temperatures in the range of about 0 ° C to 300 ° C, or more preferred be carried out at temperatures in the range of about 20 ° C to 200 ° C.

The Reaction time of the present invention varies depending on the nature of the reaction and the reaction temperature, however, may be off ranging from about several minutes to 72 hours.

To When the reaction is completed, the resulting reaction mixture is passed through conventional Treated method, whereby the target compound is obtained.

Another production method of unsaturated compounds of the present invention is one according to the following reaction:

Accordingly, become an aromatic compound (3) and a carbonyl or cyano compound (14) in the presence of a base reacted by the palladium-phosphine complex is used as a catalyst or by the palladium compound and phosphine compound of the present invention as a catalyst be used, whereby an aromatic carbonyl or cyano compound (15) is obtained.

Examples the (hetero) aryl compound of formula (3), which in the present Invention used include the same as those mentioned above.

The Compounds of formula (14) used in the present invention can be used are selected from the compounds which have a methylene group and a carboanion under the influence of a Can generate base, namely so-called active methylene compounds. Examples of such compounds include monoketones, diketones, esters, diesters, nitriles and amides. Specific examples of such compounds include acetone, 2-butanone, 2-pentanone, 3-pentanone, acetophenone, 2,4-pentanedione, 2,4-hexanedione, 1,3-cyclopentanedione, 1,3-cyclohexanedione, 1,3-diphenyl-1,3-propanedione, methyl acetate, ethyl acetate, Butyl acetate, tert-butyl acetate, phenyl acetate, ethyl butylate, ethyl isobutylate, Ethyl 2-phenylacetate, diethylsuccinate, γ-butyrolactone, dimethylmalonate, Diethyl malonate, di-tert-butyl malonate, dimethyl methyl malonate, diethyl ethyl malonate, acetonitrile, Propionitrile, butyronitrile, isobutyronitrile, malononitrile, methylmalononitrile, N, N-dimethylacetamide, N-methylacetamide, N, N-ethylacetamide, N, N-diphenylacetamide, Propionamide, N-methylpropionamide, N, N-dimethylpropionamide, β-propiolactam and N-methyl-β-propiolactam, γ-butyrolactam, without her specifically on the listed limited are.

In this production method, it is only required that not less than 1 mole of the compound (14) in the reaction system be in relation to the number m ^{1 of} the aromatic compound (3). However, it is more preferable that the compound (14) in the reaction system be in the range of 1 to 2 times molar with respect to the number m ^{1 of} the compound (3), since the recovery of the unreacted compound (14) is problematic becomes.

In this production method, the use of bases as auxiliaries is suitable. The to ver The bases used may be selected from inorganic bases and / or organic bases, without being limited to particular ones. Examples of such bases include carbonates of alkali metals or alkaline earth metals such as lithium carbonate, sodium carbonate, potassium carbonate, rubidium carbonate, cesium carbonate, magnesium carbonate, calcium carbonate, barium carbonate, etc .; Alkoxides of alkali metals such as sodium methoxide, sodium ethoxide, sodium phenoxide, sodium tert-butoxide, potassium methoxide, potassium ethoxide, potassium phenoxide, potassium tert-butoxide, lithium methoxide, lithium ethoxide, lithium phenoxide, lithium tert-butoxide, etc .; Phosphates of alkali metals such as lithium phosphate, potassium phosphate, sodium phosphate, etc .; and amines such as trimethylamine, triethylamine, triisopropylamine, tricyclohexylamine, diethylamine, diisopropylamine, etc.

The Amount of the base used is in relation to the number m of the aromatic Compound (3) in m is preferably not less than equimolar. At one equivalent the base of less than 1 mol can reduce the yield of the unsaturated Compound produced by the manufacturing process of the present Invention was reduced. Nevertheless, it even affects the addition of a large excess the base hardly adversely affects the yield of the unsaturated Compound produced by the production process of the present invention but does make up the refurbishment process Termination of the reaction problematic. Consequently, the amount is the base used, with respect to mol, more preferably in the range of 1 to 5 times.

The Production method of the above-mentioned unsaturated compounds is usually used in Presence of a solvent, that for the reaction is inert, carried out. Any solvent can without special restriction used as long as it does not seriously hinder the reaction. Examples of such solvents include aliphatic organic solvents such as pentane, hexane, Heptane, octane, etc .; alicyclic organic solvents, such as cyclohexane, Methylcyclohexane, etc., aromatic organic solvents such as benzene, toluene, Xylene, etc .; Ethers, such as diethyl ether, diisopropyl ether, dimethoxyethane, Tetrahydrofuran, dioxane, dioxolane, etc .; Acetonitrile, dimethylformamide, Dimethyl sulfoxide, hexamethyl phosphoric triamide. Be among these aromatic organic solvents, such as benzene, toluene, xylene, etc., and ethers, such as diethyl ether, dimethoxyethane, Tetrahydrofuran, dioxane, etc. stronger preferably used.

The The present invention can be carried out in an atmosphere of inert gases such as nitrogen or argon under normal pressure or under elevated pressure.

The The present invention can be carried out at temperatures in the range of about 0 ° C to 300 ° C, or more preferred be carried out at temperatures in the range of about 20 ° C to 200 ° C.

The Reaction time of the present invention varies depending on the nature of the reaction and the reaction temperature, however, may be off ranging from about several minutes to 72 hours.

To When the reaction is completed, the resulting reaction mixture is passed through conventional Treated method, whereby the target compound is obtained.

Further, one of the production methods of the unsaturated compounds of the present invention is one according to the following reaction:

A aromatic compound (3), an alcohol (16) and carbon monoxide reacted in the presence of a base by the palladium-phosphine complex of the present invention is used as a catalyst or by the palladium compound and the phosphine compound of the present Be used as a catalyst, whereby an aromatic Carbonsäureester (17) is obtained.

Examples of the aromatic compound (3) used in the present invention can be used include the same as those mentioned above. The alcohols are those with 1-4 Carbon atoms, including methanol, Ethanol, n-propanol, isopropanol, n-butanol, isobutanol and sec-butanol.

In this production process, the alcohol (16) in the reaction system must be in an amount of not less than one equimolar with respect to the number m ^{1 of} the aromatic compound (3) lie. In cases where the recovery of the unreacted alcohol (16) becomes problematic, the alcohol, in terms of moles, preferably in the reaction system is in the range of 1 to 3 times of m ^{1 of} the aromatic compound (3).

at This preparation method suitably bases as auxiliaries used. The bases to be used may be inorganic bases and / or organic bases without specific limitation. Examples of such bases include carbonates of alkali metals or Alkaline earth metals, such as lithium carbonate, sodium carbonate, potassium carbonate, Rubidium carbonate, cesium carbonate, magnesium carbonate, calcium carbonate, Barium carbonate, etc .; Alkoxides of alkali metals, such as sodium methoxide, Sodium ethoxide, sodium phenoxide, sodium tert-butoxide, potassium methoxide, Potassium ethoxide, potassium phenoxide, potassium tert-butoxide, lithium methoxide, Lithium ethoxide, lithium phenoxide, lithium tert-butoxide, etc .; alkali or alkaline earth metal hydroxides, such as sodium hydroxide, potassium hydroxide, Lithium hydroxide, barium hydroxide, etc .; Phosphates of alkali metals, such as lithium phosphate, potassium phosphate, sodium phosphate, etc .; and amines, such as trimethylamine, triethylamine, triisopropylamine, tricyclohexylamine, Diethylamine, diisopropylamine, etc .; and acetates of alkali metals such as sodium acetate, potassium acetate, lithium acetate, etc.

The amount of the base used is preferably not smaller than equimolar with respect to the number m ^{1 of} the aromatic compound (3). With one equivalent of the base of less than 1 mole, the yield of the unsaturated compound obtained by the production method of the present invention may be reduced. However, even the addition of a large excess of the base hardly affects adversely the yield of the unsaturated compound obtained by the production process of the present invention, but makes the work-up process after completion of the reaction problematic. Thus, the amount of base used, with respect to mol, is more preferably in the range of 1 to 5 times.

The Production method of the above-mentioned unsaturated compounds is usually used in Presence of a solvent, that for the reaction is inert, carried out. Although there is no specific limitation on the solvent There can be any solvent used as long as it does not seriously hinder the reaction. Examples of such a solvent include aliphatic organic solvents such as pentane, hexane, Heptane, octane, etc .; alicyclic organic solvents, such as cyclohexane, Methylcyclohexane, etc .; aromatic organic solvents, such as benzene, toluene, Xylene, etc .; Ethers, such as diethyl ether, diisopropyl ether, dimethoxyethane, Tetrahydrofuran, dioxane, dioxolane, etc .; Acetonitrile, dimethylformamide, Dimethylsulfoxide, hexamethylphosphoric triamide. Be among these aromatic organic solvents, such as benzene, toluene, xylene, etc., and ethers, such as diethyl ether, dimethoxyethane, Tetrahydrofuran, dioxane, etc. stronger preferably used.

The the present invention will become ordinary carried out under pressure with carbon monoxide. The pressure of the used Carbon monoxide ranges from about 0.1 to 30 MPa, or more preferably in the range of about 0.1 to 20 MPa.

The Reaction of the present invention can be carried out at temperatures in the range from about 0 ° C up to 300 ° C, or stronger preferably be carried out at temperatures in the range of about 20 ° C to 200 ° C.

The Reaction time of the present invention varies depending on the individual reaction and the reaction temperature, however, can be selected from a range of about several minutes to 72 hours.

To Termination of the reaction, the reaction mixture by conventional Treated method, whereby the target compound is obtained.

The Palladium-phosphine complexes used in the present invention as Catalyst can be used in catalytically active forms, even if they be prepared by a so-called in situ process, namely by the direct addition of the palladium compound and the phosphine compound to the reaction system.

Best mode for carrying out the invention

The The present invention will be described with reference to the following examples in more detail described, but the invention should not be limited thereby.

• 1) ¹H-NMR-Spektrum: ein GEMINI2000 (hergestellt von Varian Inc.) oder ein DRX-500 (hergestellt von Broker Co.); interner Standard: Tetramethylsilan.
• 2) ³¹P-NMR-Spektrum: eine DRX-500-Vorrichtung (hergestellt von Broker Co.); externer Standard: 85 Gew.-% Phosphorsäure.
• 3) Gas-Chromatograph: ein GC 353 (hergestellt von GL Science Co.); Säule: eine NB-1 (30 m × 0,25 mm) (hergestellt von GL Science Co.); interner Standard: Biphenyl.

The device used to measure each of the following physical properties in the examples is as follows:

• 1) ¹ H-NMR spectrum: a GEMINI2000 (manufactured by Varian Inc.) or a DRX-500 (manufactured by Broker Co.); internal standard: tetramethylsilane.
• 2) ³¹ P-NMR spectrum: a DRX-500 device (manufactured by Broker Co.); external standard: 85% by weight phosphoric acid.
• 3) Gas Chromatograph: a GC 353 (manufactured by GL Science Co.); Column: an NB-1 (30 m × 0.25 mm) (manufactured by GL Science Co.); internal standard: biphenyl.

example 1

Preparation of 2,2-diphenyl-1- (diphenylphosphino) -1-methylcyclopropane

(1) Preparation of 1,1-dibromo-2,2-diphenylcyclopropane

Under a nitrogen atmosphere, potassium tert-butoxide (14.8 g, 132 mmol), diphenylethylene (13.2 g, 73.3 mmol) and hexane (75 ml) were placed in a reaction flask and cooled to -5 ° C. To this was added bromoform (24.1 ml, 95.4 mmol) little by little, and the mixture was stirred at the same temperature for 30 minutes. Then, water was added to the reaction mixture, and the organic layer was extracted with toluene. The toluene extract was dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The residue was recrystallized from a mixed solvent of isopropanol and toluene to give the title compound (14.4 g, 56%) as a white crystal.
¹ H NMR _(CDCl3) δ 2.47 (s, 3H), 7.16-7.37 (m, 6H), 7.46 to 7.57 (m, 4H)

(2) Preparation of 1-bromo-2,2-diphenyl-1-methylcyclopropane

Under a nitrogen atmosphere, 1,1-dibromo-2,2-diphenylcyclopropane (10.6 g, 30.0 mmol) obtained in Example 1- (1) and THF (tetrahydrofuran, 120 ml) were placed in a reaction flask, and cooled to -70 ° C. To the mixture, n-butyllithium in hexane (20 ml, 1.57 M, 31.4 mmol) was gradually added, and the mixture was stirred at the same temperature for 30 minutes. Methyl iodide (2.1 ml, 33 mmol) was added to the reaction mixture and the resulting mixture was stirred for 30 minutes and then warmed to room temperature. Then, water was added to the reaction mixture, and the organic layer was extracted with toluene. The toluene extract was dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The residue was recrystallized from methanol to give the title compound (7.28 g, 89%) as a white crystal.
¹ H-NMR _(CDCl3) δ 1.71 (d, J = 6.3 Hz, 1H), 1.75 (s, 3H), 1.97 (d, J = 6.3 Hz, 1H), 7.10-7.56 (m, 10H)

(3) Preparation of 2,2-diphenyl-1- (diphenylphosphino) -1-methylcyclopropane

Under a nitrogen atmosphere, 1-bromo-2,2-diphenylcyclopropane (1.44 g, 5.0 mmol) and magnesium (0.134 g, 5.5 mmol) and THF (10 mL) were placed in a reaction flask. Then, a trace amount of iodine was added, and the mixture was stirred at 40 ° C for 2 hours. After cooling, copper iodide (0.961 g, 5.0 mmol) and chlorodiphenylphosphine (0.90 mL, 5.0 mmol) were added and the resulting mixture was stirred at 40 ° C for 20 hours. After cooling to room temperature, hexane (10 ml) was added to the reaction mixture and the crystal which separated out was then collected by filtration. The crystal was dissolved in toluene, washed with an aqueous 28% ammonia solution and brine, and dried over anhydrous magnesium sulfate. The solvent was then removed under reduced pressure and the concentrate was recrystallized from a mixture of methanol and toluene to give the title compound (0.98 g, 50%) as a white crystal.
¹ H-NMR _(CDCl3) δ 1.08 (d, J = 2.6 Hz, 3H), 1.55 (d / d, J = 4.8, 9.7 Hz, 1H), 2.12 (d / d, J = 4.8, 15.6 Hz, 1H), 7.08-7.59 (m, 20H);
³¹ P-NMR _(CDCl3) δ 8.29.

Example 2

Preparation of 2,2-diphenyl-1- (diisopropylphosphino) -1-methylcyclopropane

Under a nitrogen atmosphere, 1-bromo-2,2-diphenylcyclopropane (1.43 g, 5.0 mmol), magnesium (0.133 g, 5.5 mmol) and THF (10 ml) were added to a reaction flask followed by Adding one Trace amount of iodine and stirring at 40 ° C for 1.5 hours. After cooling, copper iodide (0.952 g, 5.0 mmol) and chlorodiisopropylphosphine (0.80 mL, 5.0 mmol) were added, and the resulting mixture was stirred at 40 ° C for 5 hours, followed by cooling to room temperature. The resulting mixture was diluted with hexane (20 ml) and the crystal which separated out was collected by filtration. The crystal was dissolved in toluene, and the toluene solution was washed with 28% aqueous ammonia and brine, and dried over anhydrous magnesium sulfate. Then the solvent was removed under reduced pressure to give the title compound (1.06 g, 66%) as a white crystal.
¹ H-NMR _(CDCl3) δ 1.10-1.45 (m, 16H), 2.20 to 2.46 (m, 3H), 7.12 to 7.54 (m, 10H);
³¹ P-NMR _(CDCl3) δ 22.70.

Example 3

Preparation of 2,2-diphenyl-1- (di-tert-butylphosphino) -1-methylcyclopropane

Under a nitrogen atmosphere, 1-bromo-2,2-diphenyl-cyclopropane (1.44 g, 5.0 mmol), magnesium (0.134 g, 5.5 mmol) and THF (10 mL) were added to a reaction flask, followed by adding a trace amount of iodine and stirring at 40 ° C for one hour. After cooling, copper iodide (0.962 g, 5.0 mmol), lithium bromide (0.567 g, 6.5 mmol) and chlorodi-tert-butylphosphine (0.95 mL, 5.0 mmol) were added and the resulting mixture was added Stirred 60 ° C for 3 hours, followed by cooling to room temperature. The resulting mixture was diluted with hexane (20 ml), and the crystals that separated were collected by filtration. The crystal was dissolved in toluene, and the toluene solution was washed with 28% aqueous ammonia and brine, and dried over anhydrous magnesium sulfate. The solvent was then removed under reduced pressure to give the title compound (0.83 g, 47%) as a white crystal.
¹ H-NMR _(CDCl3) δ 1.22 (d, J = 11.0 Hz, 9H), 1.23-1.39 (m, 1H), 1.31 (d, J = 10.6 Hz , 9H), 1.36 (d, J = 1.2Hz, 3H), 2.27 (d / d, J = 5.0, 12.6Hz, 1H), 7.00-7.49 ( m, 10H);
³¹ P-NMR _(CDCl3) δ 39.25.

Example 4

Preparation of 2,2-diphenyl-1- (di-tert-butylphosphino) -1-methylcyclopropane

(1) Preparation of 1-chloro-1-methyl-2,2-diphenylcyclopropane

Under a nitrogen atmosphere, 1,1-dichloroethane (30.0 g, 303 mmol), diphenylethylene (5.59 g, 31.0 mmol) and diethyl ether (62 ml) were placed in a reaction flask and cooled to -40 ° C. To the mixture, n-butyllithium in hexane (45 ml, 1.56 M, 70.2 mmol) was gradually added, and the mixture was stirred at the same temperature for one hour, followed by heating to room temperature. Then, water was added to the reaction mixture, and the organic layer was extracted with toluene. The toluene extract was dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The concentrate was recrystallized from ethanol to give the title compound (5.91 g, 78%) as a white crystal.
¹ H-NMR _(CDCl3) δ 1.57 (s, 3H), 1.67 (d, J = 6.2 Hz, 1H), 1.87 (d, J = 6.2 Hz, 1H), 7.10-7.33 (m, 6H), 7.37-7.55 (m, 4H).

(2) Preparation of 2,2-diphenyl-1- (di-tert-butyl-phosphino) -1-methylcyclopropane

Under a nitrogen atmosphere were 1-chloro-1-methyl-2,2-diphenylcyclopropane (2.43 g, 10.0 mmol), Magnesium (0.279 g, 11.5 mmol) and THF (10 mL) in a reaction flask followed by the addition of a trace amount of iodine and stirring 60 ° C for 5 hours. After cooling were copper iodide (1.92 g, 10.0 mmol), lithium bromide (0.879 g, 10.1 mmol) and chlorodi-tert-butylphosphine (2.1 mL, 11.0 mmol) were added, and the resulting mixture was stirred at 60 ° C for 3 hours, followed from cooling to room temperature. The resulting mixture was washed with hexane (20 ml), and the crystal that separated was collected by filtration. The crystal was dissolved in toluene, and the toluene solution was mixed with 28% (w / w) aqueous Ammonia and saline washed and over dried anhydrous magnesium sulfate. The solvent was reduced Removed pressure, giving the title compound (0.89 g, 25%) as a white crystal was obtained.

Example 5

Preparation of diphenyl- (4-methoxyphenyl) amine

Under a nitrogen atmosphere, diphenylamine (0.85 g, 5.0 mmol) and biphenyl as an internal standard were added to a reaction flask, followed by addition of 10 ml of toluene. To the mixture were added sodium tert -butoxide (0.58 g, 6.0 mmol), 4-bromoanisole (0.69 mL, 5.5 mmol), palladium acetate (2.8 mg, 0.0125 mmol) and 2 , 2-Diphenyl-1- (di-tert-butylphosphino) -1-methylcyclopropane (8.8 mg, 0.025 mmol) obtained in Example 4 was added, and the resulting mixture was stirred at 100 ° C for 3 hours. The reaction mixture was cooled and analyzed by gas chromatography to show the formation of the target diphenyl- (4-methoxyphenyl) amine in a yield of 95%.
¹ H-NMR _(CDCl3) δ 3.80 (s, 3H), 6.79 to 7.28 (m, 14H)

Example 6

Preparation of diphenyl- (4-methoxyphenyl) amine

To a solution from diphenylamine (0.34 g, 2.0 mmol) in 4 mL toluene was added sodium tert -butoxide (0.23 g, 2.4 mmol), 4-chloroanisole (0.27 ml, 2.2 mmol), (π-allyl) palladium chloride (3.7 mg, 0.01 mmol) and 2,2-diphenyl-1- (di-tert-butylphosphino) -1-methylcyclopropane (14.1 mg, 0.04 mmol), obtained in Example 4, added under a nitrogen atmosphere, and the mixture was for 3 hours at 100 ° C touched. The reaction mixture was cooled, washed with water and over dried anhydrous magnesium sulfate. Then the solvent became removed under reduced pressure, and the concentrate was passed through column to give the title compound (0.53 g, 95%) as a white crystal was obtained.

Example 7

Preparation of N-phenylcarbazole

To a solution of carbazole (0.34 g, 2.0 mmol) in xylene (4 mL) was added sodium tert-butoxide (0.23 g, 2.4 mmol), bromobenzene (0.23 mL, 2.2 mmol), palladium acetate (4.5 mg, 0.02 mmol) and 2,2-diphenyl-1- (di-tert-butylphosphino) -1-methylcyclopropane (14.1 mg, 0.04 mmol), obtained in Example 4, under a nitrogen atmosphere, and the mixture was stirred for 3 hours at 120 ° C. The reaction mixture was cooled, washed with water and dried over anhydrous magnesium sulfate. Then, the solvent was removed under reduced pressure, and the concentrate was purified by column chromatography, whereby N-phenylcarbazole (0.479 g, 98%, purity:> 99%) was obtained as a white crystal.
¹ H-NMR (CDCl ₃₎ δ 7.23 to 7.67 (m, 11H), 8.15 (br-d, J = 7.6 Hz, 2H).

Example 8

Preparation of 4-methoxybiphenyl

Under a nitrogen atmosphere, 4-trifluoromethanesulfonyloxyanisole (0.49 g, 1.9 mmol), phenylboronic acid (0.29 g, 2.4 mmol), potassium fluoride (0.24 g, 4.2 mmol), (π-allyl) palladium chloride (3.6 mg, 0.01 mmol), 2,2-diphenyl-1- (di-tert-butylphosphino) -1-methylcyclopropane (14.0 mg, 0.04 mmol), obtained in Example 4, and Toluene (4 ml) was added to a reaction flask and stirred for 1.5 hours at 80 ° C. The reaction mixture was cooled, washed with water and dried over anhydrous magnesium sulfate. Then, the solvent was removed under reduced pressure, and the concentrate was purified by column chromatography, whereby the title compound (0.34 g, 96%) was obtained as a white crystal.
¹ H-NMR _(CDCl3) δ 3.85 (s, 3H), 6.93-7.04 (m, 2H), 7.23 to 7.69 (m, 7H).

Example 9

Preparation of 4-methoxybiphenyl

Under a nitrogen atmosphere were added 4-chloroanisole (0.30 g, 2.1 mmol), phenyl boronic acid (0.37 g, 3.0 mmol), potassium phosphate n-hydrate (0.85 g), (π-allyl) palladium chloride (3.7 mg, 0.01 mmol), 2,2-diphenyl-1- (di-tert-butylphosphino) -1-methylcyclopropane (14.1 mg, 0.04 mmol), obtained in Example 4, and toluene (4 ml) in a reaction flask and stirred for 3 hours at 80 ° C. The reaction mixture was drained cooled, washed with water and dried over anhydrous magnesium sulfate. Then, the solvent was removed under reduced pressure, and the concentrate was purified by column chromatography, whereby the title compound (0.35 g, 90%) was obtained as a white crystal.

Example 10

Preparation of [2,2-diphenyl-1- (di-tert-butylphosphino) -1-methylcyclopropane] (π-allyl) palladium chloride

Under a nitrogen atmosphere, (π-allyl) palladium chloride dimer (0.183 g, 0.5 mmol), 2,2-diphenyl-1- (di-tert-butyl-phosphino) -1-methylcyclopropane (0.352 g, 1.0 mmol) and 3 ml of toluene in a reaction flask, and the mixture was stirred at room temperature for 6 hours. The crystal which separated out was filtered and dried to give the title compound (0.490 g, 91%).
¹ H-NMR (CDCl ₃₎ δ 1.01 to 1.16 (m, 1H), 1.34 to 1.71 (m, 10H), 1.43 (d, J = 5.2 Hz, 3H) , 1.47 (d, J = 12.8 Hz, OH), 2.28-3.10 (m, 1H), 3.35 (br-s, 1H), 3.96 (br-d, J = 16.4 Hz, 1H), 4.35 (br-s, 1H), 5.26 (br-s, 1H), 6.92-7.06 (m, 1H), 7.08-7, 47 (m, 7H), 7.68-7.84 (m, 2H);
³¹ P-NMR _(CDCl3) δ 75.63.

Industrial applicability

The Phosphine compounds of the present invention form with palladium compounds Palladium-phosphine complexes that have high activity as a catalyst for linking reactions unsaturated compounds and aromatic compounds.

Claims (10)

Phosphine compound of the formula (1),

wherein R ^{1 is} a hydrogen atom, an alkyl group, a cycloalkyl group or a phenyl group which may be substituted; R ² and R ³ are the same or different, an alkyl group, a cycloalkyl group or a phenyl group which may be substituted; R ⁴ and R ⁵ , each same or different, are a hydrogen atom, an alkyl group, a cycloalkyl group or a phenyl group which may be substituted; R ⁶ , R ⁷ , R ⁸ and R ^{9 are} each the same or different, an alkyl group, a cycloalkyl group, a phenyl group which may be substituted, an alkoxyl group, a dialkylamino group, a halogen atom, a benzyl group, a naphthyl group or a halogenated alkyl group ; R ⁶ and R ⁷ or R ⁸ and R ^{9 may} each be combined to form a fused ring, a trimethylene group, a tetramethylene group or a methylenedioxy group; p, q, r and s are each an integer from 0 to 5; and p + q and r + s are each in the range of 0 to 5. Palladium-phosphine complex formed by reacting the Phosphine compound according to claim 1 with a palladium compound can be obtained. Palladium-phosphine complex according to claim 2, wherein the palladium compound is a palladium salt or a palladium complex wherein the valence of palladium is 4, 2 or 0. Preparation process of an unsaturated compound or an aromatic compound under Ver Use of the palladium-phosphine complexes mentioned in claim 2 or 3 as catalyst. Preparation process of an unsaturated compound or a aromatic compound using the recited in claim 1 Phosphine compound and a palladium compound. The production method according to claim 4 or 5, which comprises reacting a compound represented by the following formula (3) or (4): Ar ¹ (X ¹ ) m ¹ (3)

wherein in formula (3) Ar ^{1 is} an aryl group which may be substituted or a heteroaryl group which may be substituted; X ^{1 is} a chlorine atom, a bromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, a methanesulfonyloxy group or a para-toluenesulfonyloxy group, and m ^{1 is} an integer of 1 to 4, and in formula (4) R ¹⁰¹ , R ¹¹¹ and R ¹²¹ each the same or different, a hydrogen atom, an alkyl group, an aryl group which may be substituted, a heteroaryl group which may be substituted, an alkoxycarbonyl group or a cyano group; X ^{11 is} a chlorine atom, a bromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, a methanesulfonyloxy group or a para-toluenesulfonyloxy group, with a compound represented by the following formula (5) or (6) Ar ² X ² (5)

wherein in formula (5) Ar ^{2 is} an aryl group which may be substituted or a heteroaryl group which may be substituted; X ² B (OR ¹³ ) (OR ¹⁴ ), Sn (R ¹⁵ ) ₃ , MgX, ZnX, Al (R ¹⁵ ) ₂ or Li, and in formula (6) R ¹⁰ , R ¹¹ and R ¹² , are the same or differently, a hydrogen atom, an alkyl group, an aryl group which may be substituted, a heteroaryl group which may be substituted, an alkoxycarbonyl group or a cyano group; R ¹⁰ and R ¹² can be combined to form a single bond that forms a triple bond together with the existing double bond; X ^{3 is} a hydrogen atom, B (OR ¹³ ) (OR ¹⁴ ), Sn (R ¹⁵ ) ₃ , MgX, ZnX, Al (R ¹⁵ ) ₂ or Li; R ¹³ and R ¹⁴ , each same or different, are a hydrogen atom, an alkyl group or combined to form an ethylene group or a 1,2-dimethylethylene group; R ^{15 is} an alkyl group and X is a chlorine atom, a bromine atom or an iodine atom to give a compound of the formula (7), (8), (9) or (10) Ar ¹ - (Ar ² ) m ² (7)

wherein Ar ¹ , Ar ² , R ¹⁰ , R ¹¹ , R ¹² , R ¹⁰¹ , R ¹¹¹ and R ^{121 are} as defined above and m ^{2 is} an integer of 1 to 4. The production method according to claim 4 or 5, which comprises reacting a compound represented by the following formula (3) or (4) Ar ¹ (X ¹ ) m ¹ (3)

wherein in formula (3) Ar ^{1 is} an aryl group which may be substituted or a heteroaryl group which may be substituted; X ^{1 is} a chlorine atom, a bromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, a methanesulfonyloxy group or a para-toluenesulfonyloxy group, and m ^{1 is} an integer of 1 to 4, and in formula (4) R ¹⁰¹ , R ¹¹¹ and R ¹²¹ each the same or different, a hydrogen atom, an alkyl group, an aryl group which may be substituted, a heteroaryl group which may be substituted, an alkoxycarbonyl group or a cyano group; X ^{11 is} a chlorine atom, a bromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, a methanesulfonyloxy group or a para-toluenesulfonyloxy group, with an oxygen compound or a nitrogen compound represented by the following formula (11) R ¹⁶ -OH (11) wherein R ^{16 is} an alkyl group, an aryl group which may be substituted, or a heteroaryl group which may be substituted; Q is an oxygen atom,

wherein R ¹⁷ , R ¹⁸ and R ^{19 are} a hydrogen atom, an alkyl group, an aryl group which may be substituted, or a heteroaryl group which may be substituted; and R ¹⁶ and R ¹⁷ can be combined to form a divalent aromatic ring which may be substituted, to obtain a compound of the following formula (12) or (13) Ar ¹ (QR ¹⁶ ) m ³ (12)

wherein Ar ¹ , Q, R ¹⁶ , R ¹⁰¹ , R ¹¹¹ and R ^{121 are} as defined above and m ^{3 is} an integer of 1 to 4. A production process according to claim 4 or 5, which comprises reacting an aromatic compound of the formula (3) Ar ¹ (X ¹ ) _m ¹ (3) wherein Ar ^{1 is} an aryl group which may be substituted or a heteroaryl group which may be substituted; X ^{1 is} a chlorine atom, a bromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, a methanesulfonyloxy group or a para-toluenesulfonyloxy group, and m ^{1 is} an integer of 1 to 4, with a carbonyl compound or a cyano compound of the formula (14) R ¹⁸ -CH ₂ -R ¹⁹ (14) wherein R ^{18 is} a hydrogen atom, CO ₂ R ²⁰ , C (= O) R ²¹ or a cyano group; R ^{19 is} CO ₂ R ²² , C (= O) R ²³ or a cyano group; R ²⁰ , R ²¹ , R ²² and R ^{23 are} each an alkyl group, an aryl group which may be substituted, or a heteroaryl group which may be substituted to give a compound of the formula (15)

wherein Ar ¹ , R ¹⁸ and R ^{19 are} as defined above and m ^{4 is} an integer of 1 to 4. A production process according to claim 4 or 5, which comprises reacting an aromatic compound of the formula (3) Ar ¹ (X ¹ ) _m ¹ (3) wherein Ar ^{1 is} an aryl group which may be substituted or a heteroaryl group which may be substituted; X ^{1 is} a chlorine atom, a bromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, a methanesulfonyloxy group or a para-toluenesulfonyloxy group, and m ^{1 is} an integer of 1 to 4, with carbon monoxide and an alcohol of the formula (16) R ²⁴ OH (16) wherein R ^{24 is} an alkyl group to obtain a carboxylic acid ester of the formula (17) Ar ¹ (CO ₂ R ²⁰ ) m ⁵ (17) wherein Ar ¹ and R ^{24 are} as defined above and m ^{5 is} an integer of 1 to 4. Production process of unsaturated compounds according to any one of claims 4 to 9, which is the Carry out the reaction in the presence of a base.